The Developmental vitamin D model (DVD) as an animal model for schizophrenia

大多数澳大利亚人都有机会享受阳光带来的自然好处，然而许多澳大利亚人缺乏维生素D。我们已经证明，即使在被称为“阳光之州”的昆士兰州，隆冬时节的维生素D水平也低于世界卫生组织建议的水平。我们正在探索低维生素D作为世界范围内普遍现象的生物学解释，即在一年中较冷的月份出生的精神分裂症患者的发病率增加了7-10%。精神分裂症是一种出现在青春期的发育性疾病，影响着世界上约1%的人口。到目前为止，我们已经证明，怀孕期间血液中维生素D含量低或维生素D摄入量不足的母亲的后代患精神分裂症的几率会增加。因此，早期的迹象似乎很有希望，但显然需要更多的研究来证实这一观点。我们对动物的研究表明，通过限制怀孕大鼠的维生素D摄入量，新生儿的大脑发育会有所不同。最明显的是侧脑室体积增加，这是精神分裂症患者的一个关键解剖发现。当这些动物成年后，侧脑室的增加仍然存在。此外，当我们探索这些动物的行为时，我们发现它们在学习和记忆方面的缺陷与许多精神分裂症患者相似。此外，当我们将这些动物暴露于诱发精神病或阻断患者精神病的药物中时，我们发现在子宫内被剥夺这种维生素的动物的敏感性更高，特别是在运动中。这些行为发现与精神分裂症的最佳动物模型一致。在机制层面上，它们表明大脑中两种主要的神经递质异常，多巴胺和谷氨酸一直与这种疾病有关。本应用程序中概述的实验将试图为这些改变的行为建立神经化学基础。

Most Australians have the opportunity to enjoy the natural benefits of sunlight, however many Australians lack vitamin D. We have shown that even in Queensland, the so-called Sunshine State, vitamin D levels in the middle of winter are below World Health Organisation recommended levels. We are exploring low maternal vitamin D as a biological explanation for the universal phenomena worldwide of a 7-10% increase in the incidence of patients born with schizophrenia in the colder months of the year. Schizophrenia is a developmental disease that presents in adolescence and affects about 1% of the world's population. To date we have shown increased amounts of schizophrenia in offspring from mothers that had low blood vitamin D levels during pregnancy or who had inadequate vitamin D intake. Early signs therefore appear promising but obviously more research is required to confirm this idea. Our studies in animals have revealed that by restricting vitamin D intake in pregnant rats, newborns have brains that develop differently. Most notably lateral ventricle volume is increased, a key anatomical finding in patients with schizophrenia. When these animals become adults the increase in lateral ventricles persists. Also when we explore the behaviour of these animals we find a deficit in learning and memory similar to that seen in many schizophrenic patients. Furthermore when we expose these animals to agents that induce psychosis or agents that block psychosis in patients we see a heightened sensitivity in animals that were deprived of this vitamin in utero particularly in locomotion. These behavioural findings are consistent with the best animal models for schizophrenia. At a mechanistic level they indicate an abnormality in the two major neurotransmitters in the brain that have been consistently linked with this disease, dopamine and glutamate. The experiments outlined in this application will attempt to establish the neurochemical basis for these altered behaviours.